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Cocaine self-administration in dopamine-transporter knockout mice
B A Rocha1, F Fumagalli, R R Gainetdinov
1Department of Pharmacology, University of North Texas Health Science Center, Fort Worth 76107, USA.
Nature Neuroscience
|April 9, 1999
Summary
Cocaine addiction may involve more than just the dopamine system. Even without the dopamine transporter (DAT), mice still self-administer cocaine, suggesting other brain pathways, like those involving serotonin, play a role.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- The plasma membrane dopamine transporter (DAT) clears dopamine from synapses.
- Cocaine blocks DAT, increasing extracellular dopamine, which is thought to cause addiction.
- This study investigates if cocaine's addictive properties depend solely on DAT.
Purpose of the Study:
- To determine if cocaine self-administration occurs in mice lacking the dopamine transporter (DAT).
- To explore the neurobiological mechanisms underlying cocaine's effects independent of DAT.
Main Methods:
- Utilized genetically engineered mice lacking the dopamine transporter (DAT).
- Administered cocaine to DAT-deficient mice to assess self-administration behavior.
- Mapped cocaine binding sites and neuronal activation patterns in the brain.
Main Results:
- Mice without DAT still self-administered cocaine, despite high baseline extracellular dopamine.
- Cocaine binding and neuronal activation were observed in brain regions beyond the dopaminergic system.
- Evidence suggests involvement of serotonergic pathways in cocaine self-administration.
Conclusions:
- Cocaine's reinforcing and addictive properties are not exclusively mediated by the dopamine transporter (DAT).
- Targets other than DAT, potentially including the serotonin transporter, can initiate and sustain cocaine self-administration.
- Serotonergic brain regions may play a significant role in mediating cocaine's effects in the absence of DAT.